The evidence base of US Food and Drug Administration approvals of novel cancer therapies from 2000 to 2020.

Concerns have been raised that regulatory programs to accelerate approval of cancer drugs in cancer may increase uncertainty about benefits and harms for survival and quality of life (QoL). We analyzed all pivotal clinical trials and all non-pivotal randomized controlled trials (RCTs) for all cancer drugs approved for the first time by the FDA between 2000 and 2020. We report regulatory and trial characteristics.

Examination of Impact of After-Hours Admissions on Hospital Resource Use, Patient Outcomes, and Costs.

Background: Nighttime and weekends in hospital and intensive care unit (ICU) contexts are thought to present a greater risk for adverse events than daytime admissions. Although some studies exist comparing admission time with patient outcomes, the results are contradictory. No studies currently exist comparing costs with the time of admission.

The impact of Stress Management and Resilience Training (SMART) on academic physicians during the implementation of a new Health Information System: An exploratory randomized controlled trial.

Objective: The Stress Management and Resilience Training (SMART) program is an evidence-based intervention designed to build resilience in physicians in clinical practice. The objective of the current study was to assess the impact of the SMART program on academic physicians' levels of resilience, subjective happiness, stress, and anxiety, and specifically during the implementation of a new hospital-wide Health Information System (HIS).

Methods: A total of 40 physicians in a tertiary care academic hospital were randomized (allocation ratio 1:1) to either the SMART intervention or the control condition.

NFAT5/TonEBP Limits Pulmonary Vascular Resistance in the Hypoxic Lung by Controlling Mitochondrial Reactive Oxygen Species Generation in Arterial Smooth Muscle Cells.

Chronic hypoxia increases the resistance of pulmonary arteries by stimulating their contraction and augmenting their coverage by smooth muscle cells (SMCs). While these responses require adjustment of the vascular SMC transcriptome, regulatory elements are not well defined in this context. Here, we explored the functional role of the transcription factor nuclear factor of activated T-cells 5 (NFAT5/TonEBP) in the hypoxic lung.

RGS5 Attenuates Baseline Activity of ERK1/2 and Promotes Growth Arrest of Vascular Smooth Muscle Cells.

The regulator of G-protein signaling 5 (RGS5) acts as an inhibitor of Gα and Gα activity in vascular smooth muscle cells (VSMCs), which regulate arterial tone and blood pressure. While RGS5 has been described as a crucial determinant regulating the VSMC responses during various vascular remodeling processes, its regulatory features in resting VSMCs and its impact on their phenotype are still under debate and were subject of this study. While shows a variable expression in mouse arteries, neither global nor SMC-specific genetic ablation of affected the baseline blood pressure yet elevated the phosphorylation level of the MAP kinase ERK1/2.

Glycyrrhetinic Acid Antagonizes Pressure-Induced Venous Remodeling in Mice.

Development of spider veins is caused by the remodeling of veins located in the upper dermis and promoted by risk factors such as obesity or pregnancy that chronically increase venous pressure. We have repeatedly shown that the pressure-induced increase in biomechanical wall stress is sufficient to evoke the formation of enlarged corkscrew-like superficial veins in mice. Subsequent experimental approaches revealed that interference with endothelial- and/or smooth muscle cell (SMC) activation counteracts this remodeling process.

Magnolol inhibits venous remodeling in mice.

Due to gravity the venous vasculature in the lower extremities is exposed to elevated pressure levels which may be amplified by obesity or pregnancy. As a consequence, venules dilate and may be slowly transformed into varicose or spider veins. In fact, chronically elevated venous pressure was sufficient to cause the corkscrew-like enlargement of superficial veins in mice.

Varicose Remodeling of Veins Is Suppressed by 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Inhibitors.

Background: Despite the high prevalence of chronic venous insufficiency and varicose veins in the Western world, suitable pharmaceutical therapies for these venous diseases have not been explored to date. In this context, we recently reported that a chronic increase in venous wall stress or biomechanical stretch is sufficient to cause development of varicose veins through the activation of the transcription factor activator protein 1.

Methods And Results: We investigated whether deleterious venous remodeling is suppressed by the pleiotropic effects of statins.

5Z-7-Oxozeanol Inhibits the Effects of TGFβ1 on Human Gingival Fibroblasts.

Transforming growth factor (TGF)β acts on fibroblasts to promote the production and remodeling of extracellular matrix (ECM). In adult humans, excessive action of TGFβ is associated with fibrotic disease and fibroproliferative conditions, including gingival hyperplasia. Understanding how the TGFβ1 signals in fibroblasts is therefore likely to result in valuable insights into the fundamental mechanisms underlying fibroproliferative disorders.